Benefits of a ketogenic diet in MS

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Benefits of a ketogenic diet in MS

Postby frodo » Sat Jan 02, 2016 6:35 am

Something that should be read

http://www.hindawi.com/journals/msi/2015/681289/

An extract from the text:

9. The Effect of the Ketogenic Diet on Oxidative Stress

A ketogenic diet has been shown to reduce the generation of reactive oxygen species through its effect on uncoupling proteins. It also increases levels of antioxidant agents including catalase and glutathione through its inhibitory action on histone deacetylases and activation of the Nrf2 pathway.

9.1. The Ketogenic Diet Increases Mitochondrial Uncoupling Protein Levels

The process of oxidative phosphorylation generates reactive oxygen species. The extent of reactive oxygen species generation correlates strongly with the potential difference across the inner mitochondrial membrane. Uncoupling proteins (UCPs) can reduce this potential difference by allowing the entry of protons into the mitochondrial matrix. Although this “mild” uncoupling may incur a small reduction in ATP generated through oxidative phosphorylation, its overall net effect is to enhance respiration and ATP levels through a reduction in reactive oxygen species formation and protection from apoptotic events [64]. A ketogenic diet appears to promote UCP activity, specifically the activity of UCP2, UCP4, and UCP5 with a corresponding decline in reactive oxygen species [65].

9.2. Ketones Inhibit Histone Deacetylases

The ketone beta-hydroxybutyrate has a direct, dose-dependent inhibitory activity on class I histone deacetylases (HDACs) including HDAC1, HDAC3, and HDAC4. The ketone acetoacetate has also been shown to inhibit class I and class IIa HDACs. Beta-hydroxybutyrate’s inhibition of HDAC promotes the acetylation of histone H3 lysine 9 and histone H3 lysine 14 and increases the transcription of genes regulated by FOXO3A. These include genes leading to the expression of the antioxidant enzymes mitochondrial superoxide dismutase and catalase [66].

9.3. A Ketogenic Diet Leads to the Activation of the Nrf2 Pathway

The ketogenic diet raises glutathione levels in the hippocampus of rats [67]. This is thought to occur through the Nrf2 (nuclear factor erythroid 2-related factor) pathway. When the ketogenic diet is first initiated, there is a temporary increase in oxidative stress. This may be activating Nrf2, since, a week after the temporary rise in oxidative stress, there is increased expression of Nrf2. Three weeks after the start of the diet, oxidative stress declines to below baseline levels and Nrf2 remains raised [68].
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